A Study Measuring Substances Potentially Indicating Bone Problems in Adults With Type 1 Gaucher Condition

Validation of a Set of Potential Biomarkers Predictive of Bone Complications in Type 1 Gaucher Disease Patients

Substances in the body, so-called biomarkers, can help predict the severity of Gaucher disease (GD)-related bone problems in adults. The main aim of the study is to determine if certain biomarkers found in the body at the time of diagnosing GD can help predict the risk of bone problems after 4-5 years.

There is no treatment involved in this study. The study will review previously collected participants' data using a database. Data from both adults with type 1 Gaucher condition as well as healthy adults will be compared.

Study Overview

• Status: Active, not recruiting
• Conditions: Gaucher Disease
• Intervention / Treatment: Other: No Intervention

Detailed Description

This is a non-interventional and retrospective study of participants with GD1 and healthy participants whose data is available in the Aragon Health Systems Biobank (BSSA) from the date of diagnosis to 4-5 years after diagnosis. The main objective of this study is to validate the prognosis value of a set of potential biomarkers related to bone disease in participants with GD1.

The study will enroll approximately 120 participants, and it would be divided into 4 groups as given below:

• Group A: GD1 with Low-Normal Bone Disease
• Group B: GD1 with Mild Bone Disease
• Group C: GD1 with Severe Bone Disease
• Group D: Healthy Participants

This study will have a retrospective data collection from the date of diagnosis of GD1 until 4-5 years from diagnosis by using data available in BSSA.

This single-centre trial will be conducted in Spain. The overall time for data collection in this study will be approximately 9 months.

• Study Type: Observational
• Enrollment (Actual): 125

Contacts and Locations

• Study Contact: Name: Takeda Contact; Phone Number: +1-877-825-3327; Email: medinfoUS@takeda.com

Study Locations

• Spain
  • Aragon
    • Zaragoza, Aragon, Spain, 50006
      • Fundación Española para el Estudio y Tratamiento de la Enfermedad de Gaucher (FEETEG)
      • Contact: Pilar Giraldo Castellano, Dr; Phone Number: +34 670 285 339; Email: giraldocastellano@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Participants diagnosed with GD1 and healthy participants in Spain.

Description

For Participants with GD1:

Inclusion Criteria

• Participants with confirmed diagnosis of GD1.
• Determination of Glucocerebrosidase (GCase) blood activity at diagnosis of GD1.
• DNA analysis result demonstrating pathogenic variants in the Glucocerebrosidase gene (GBA1) gene.
• Available data of clinical state at diagnosis and at 4-5 years from diagnosis, including S-MRI, Dual energy x-ray absorptiometry (DXA), and GD1 severity scoring system (GD1-DS3) indexes (or data to calculate it).

Exclusion Criteria

• Evidence of hepatitis B, hepatitis C infection or other chronic infectious diseases.

For Healthy Volunteers

Exclusion Criteria

• Evidence of hepatitis B, hepatitis C infection or other chronic infectious diseases.
• Evidence of bone disease.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A: GD1 with Low-normal Bone Disease; Participants with GD1 with low-normal bone disease whose samples are available for analysis in BSSA will be collected retrospectively up to approximately 5 years from diagnosis.	Other: No Intervention; As this is an observational study, no intervention will be administered.
Group B: GD1 with Mild Bone Disease; Participants with GD1 with mild bone disease whose samples are available for analysis in BSSA will be collected retrospectively up to approximately 5 years from diagnosis.	Other: No Intervention; As this is an observational study, no intervention will be administered.
Group C: GD1 with Severe Bone Disease; Participants with GD1 with severe bone disease whose samples are available for analysis in BSSA will be collected retrospectively up to approximately 5 years from diagnosis.	Other: No Intervention; As this is an observational study, no intervention will be administered.
Group D: Healthy Participants; Healthy Participants whose samples are available for analysis in BSSA will be collected retrospectively up to approximately 5 years.	Other: No Intervention; As this is an observational study, no intervention will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Biomarker Level in Participants with GD1 at 4-5 years From Diagnosis Assessed per Spanish-Magnetic Resonance Imaging (S-MRI)	Areas like spine, pelvis, and femora will be evaluated and the MRI pattern will be ranged as normal=0, non-homogenous reticular pattern=1, non-homogenous mottled pattern= 2, non-homogenous diffuse pattern= 3, and homogenous pattern=4, and the presence of complications adds a value of 4. For each site, the maximum possible value assigned is 8, and the S-MRI is the sum of the score obtained at each site; thus, the S-MRI score ranges from 0 to 24.	Baseline up to approximately 4-5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Biomarker Level in Participants with GD1 at Diagnosis as Assessed per S-MRI	Areas like spine, pelvis, and femora will be evaluated and the MRI pattern will be ranged as normal=0, non-homogenous reticular pattern=1, non-homogenous mottled pattern= 2, non-homogenous diffuse pattern= 3, and homogenous pattern=4, and the presence of complications adds a value of 4. For each site, the maximum possible value assigned is 8, and the S-MRI is the sum of the score obtained at each site; thus, the S-MRI score ranges from 0 to 24.	Baseline (At diagnosis prior to treatment start)
Change in Biomarker Level At Diagnosis And Severity Of Bone Disease At Diagnosis As Assessed Per S-MRI in Participants with GD1 and no Bone Disease in Healthy Volunteers		Baseline (At diagnosis prior to treatment start)
Change in Biomarker Level At Diagnosis And Severity Of Bone Disease At Diagnosis As Assessed Per DXA in Participants with GD1 and no Bone Disease in Healthy Volunteers		Baseline (At diagnosis prior to treatment start)
Change in Biomarker Level at Diagnosis as Assessed per Gaucher Disease Type 1 Severity Scoring System (GD1-DS3) Score in Participants with GD1	GD1-DS3 score ranges from 0 to a maximum of 19 for the disease domains bone (lytic lesions, AVN or pathological fractures, bone/joint pain, bone crisis, bone marrow infiltration, bone mineral density), hematology (thrombocytopenia, bleeding and anaemia) and visceral (splenomegaly, hepatomegaly, and Gaucher-related pulmonary disease). GD1-DS3 total score is a sum of the above three disease domain scores ranging from 0-3= borderline to mild disease, 3-6= moderate disease, 6-9= Marked disease, and +9=Severe disease.	Baseline (At diagnosis prior to treatment start)
Change in Biomarker Level at 4-5 years from Diagnosis as Assessed per GD1-DS3 Score in Participants with GD1	GD1-DS3 score ranges from 0 to a maximum of 19 for the disease domains bone (lytic lesions, AVN or pathological fractures, bone/joint pain, bone crisis, bone marrow infiltration, bone mineral density), hematology (thrombocytopenia, bleeding and anaemia) and visceral (splenomegaly, hepatomegaly, and Gaucher-related pulmonary disease). GD1-DS3 total score is a sum of the above three disease domain scores ranging from 0-3= borderline to mild disease, 3-6= moderate disease, 6-9= Marked disease, and +9=Severe disease.	Baseline to approximately 4-5 years
Comparison Between in lyso-Gb1, ChT, CCL18, and Study Biomarkers Levels in Participants with GD1 and Healthy Volunteers at Diagnosis		Baseline (At diagnosis prior to treatment start)
Comparison Between in lyso-Gb1, ChT, CCL18, and Study Biomarkers Levels in Participants with GD1 and Healthy Volunteers at 4-5 years at Diagnosis		Baseline to approximately 4-5 years
Change From Baseline in lyso-Gb1, ChT, CCL18, and Study Biomarkers Levels in Participants with GD1 and Healthy Volunteers at Diagnosis		Baseline (At diagnosis prior to treatment start)
Change From Baseline in lyso-Gb1, ChT, CCL18, and Study Biomarkers Levels in Participants with GD1 at years at Diagnosis		Baseline to approximately 4-5 years
Change From Baseline in Lumbar DXA Measurements: Bone Mineral Density (BMD), Z- score from Diagnosis	Bone mineral density of the lumbar spine would be measured by dual energy x-ray absorptiometry (DXA), and the results would be converted to Z-scores appropriate for age, sex, and race. The Z-score indicated the number of standard deviations away from a reference population in the same age range, race and with the same sex. A Z-score of 0 was equal to the mean. Negative numbers indicated values lower than the mean and positive numbers indicated values higher than the mean.	Baseline and up to approximately 4-5 years
Change From Baseline in Lumbar DXA Measurements: Bone Mineral Density (BMD), T- score from Diagnosis	BMD T-score is the standard deviation of the difference between measured BMD and that of the healthy young adult "normal". The T-score scale was as follows: -1 and above=normal, -1 to -2.5=osteopenia (below normal and may lead to osteoporosis), and -2.5 and below=osteoporosis.	Baseline and up to approximately 4-5 years

Collaborators and Investigators

• Sponsor: Takeda
• Investigators: Study Director: Study Director, Takeda

Publications and helpful links

Helpful Links

• To obtain more information on the study, click here/on this link

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2023
• Primary Completion (Estimated): May 31, 2024
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: January 18, 2023
• First Submitted That Met QC Criteria: January 18, 2023
• First Posted (Actual): January 27, 2023

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Drug Therapy
• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Lipid Metabolism Disorders; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Sphingolipidoses; Lysosomal Storage Diseases, Nervous System; Lipidoses; Lipid Metabolism, Inborn Errors; Gaucher Disease
• Other Study ID Numbers: TAK-669-5010

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• IPD Sharing Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No